Therapeutic Drug Monitoring In Practice Research Articles

Removing the physician from the equation: Patient-controlled, home-based therapeutic drug self-monitoring of tacrolimus.

The dosing of tacrolimus, which forms the backbone of immunosuppressive therapy after kidney transplantation, is complex. This is due to its variable pharmacokinetics (both between and within individual patients), narrow therapeutic index, and the severe consequences of over- and underexposure, which may cause toxicity and rejection, respectively. Tacrolimus is, therefore, routinely dosed by means of therapeutic drug monitoring (TDM). TDM is performed for as long as the transplant functions and frequent and often lifelong sampling is therefore the rule. This puts a significant burden on patients and transplant professionals and is associated with high healthcare-associated costs. Furthermore, by its very nature, TDM is reactive and has no predictive power. Finally, the current practice of TDM does not foresee in an active role for patients themselves. Rather, the physician or pharmacist prescribes the next tacrolimus dose after obtaining the concentration measurement test results. In this article, we propose a strategy of patient-controlled, home-based, self-TDM of the immunosuppressant tacrolimus after transplantation. We argue that with the combined use of population tacrolimus pharmacokinetic models, home-based sampling by means of dried blood spotting and implementation of telemedicine, this may become a feasible approach in the near future.

Best Practice for Therapeutic Drug Monitoring of Infliximab: Position Statement from the International Association of Therapeutic Drug Monitoring and Clinical Toxicology.

Infliximab, an anti-tumor necrosis factor monoclonal antibody, has revolutionized the pharmacological management of immune-mediated inflammatory diseases (IMIDs). This position statement critically reviews and examines existing data on therapeutic drug monitoring (TDM) of infliximab in patients with IMIDs. It provides a practical guide on implementing TDM in current clinical practices and outlines priority areas for future research. The endorsing TDM of Biologics and Pharmacometrics Committees of the International Association of TDM and Clinical Toxicology collaborated to create this position statement. Accumulating data support the evidence for TDM of infliximab in the treatment of inflammatory bowel diseases, with limited investigation in other IMIDs. A universal approach to TDM may not fully realize the benefits of improving therapeutic outcomes. Patients at risk for increased infliximab clearance, particularly with a proactive strategy, stand to gain the most from TDM. Personalized exposure targets based on therapeutic goals, patient phenotype, and infliximab administration route are recommended. Rapid assays and home sampling strategies offer flexibility for point-of-care TDM. Ongoing studies on model-informed precision dosing in inflammatory bowel disease will help assess the additional value of precision dosing software tools. Patient education and empowerment, and electronic health record-integrated TDM solutions will facilitate routine TDM implementation. Although optimization of therapeutic effectiveness is a primary focus, the cost-reducing potential of TDM also merits consideration. Successful implementation of TDM for infliximab necessitates interdisciplinary collaboration among clinicians, hospital pharmacists, and (quantitative) clinical pharmacologists to ensure an efficient research trajectory.

Therapeutic monitoring of anti-seizure medications in low- and middle-income countries: a systematic review

Background The treatment gap for epilepsy is large in low- and middle-income countries (LMICs) and the effectiveness and safety of the available anti-seizure medication (ASMs) is not fully understood. We systematically reviewed available evidence on therapeutic drug monitoring (TDM) of ASM in LMIC. Methods We searched four main databases (PubMed, Psych-Info, CINAHL and Embase) up to 31st December 2020, with eligible articles screened using a PRISMA checklist and a set of exclusion and inclusion criteria. Full texts were examined to evaluate the extent and practice of TDM in LMICs. Analyses were performed using Stata 13 and descriptive statistics were used to pool median distribution of TDM across studies. Results Of the 6,309 articles identified in the initial search, 65 (1.0%) met the eligibility criteria. TDM of ASMs was mostly done to assess toxicity (42.8%), but rarely to monitor adherence (9.0%). TDM differed by economic status and infrastructural status with majority of the studies coming from Europe (53.8%) and upper-middle-income countries (87.6%). First generation ASMs (82.3%) were more likely to be monitored than second generation ASMs (17.6%) and carbamazepine was the most frequently monitored drug. Fluorescence Polarization Immunoassay (FPIA) was the most common technique used for TDM (41.5%) followed by High-Performance Liquid Chromatography (HPLC) (16.9%). In addition, FPIA was the cheapest method of TDM based on approximated costs ($1000, TDx system). Assay validation and quality control were reported variably, and reference ranges used during TDM of ASMs were relatively uniform. Conclusions TDM is mostly done to evaluate ASM toxicity, but rarely for other reasons such as evaluating adherence or assessing clinical efficacy. There is a need for more investment in comprehensive and targeted TDM in LMICs when initiating treatment, switching therapies, adding or removing ASM and evaluating treatment response and safety of both first generation and second generation ASMs.

Simultaneous quantification of 55 psychotropic drugs and metabolites in human plasma with a fast UPLC-MS/MS method

ObjectivesTherapeutic drug monitoring is strongly recommended for psychotropic drugs, which present a strong inter- and intra-individual variability due to multiple factors like inflammatory state, smoking, diet, drug interactions due to polypharmacy, and genetic profile. The aim of this study was to develop and validate a fast, simple, and sensitive method allowing the simultaneous quantification of a large number of psychotropic drugs. MethodsAfter a simple sample preparation with a one-step protein precipitation, a total of 55 compounds, including 22 antidepressants, 18 antipsychotics, 2 other psychotropic drugs (bupropion and nefopam), and their metabolites, was separated on a Waters Acquity HSS T3 ultra-performance liquid chromatography column, and subsequently detected and quantified by a triple quadrupole Quantis mass spectrometer with electrospray ionization operated in positive mode. ResultsTotal run time was only 5.7 min. Limits of detection ranged from 0.01 to 0.18 µg/L depending on compound. Measuring ranges were from 0.195 to 1000 µg/L depending on compound, and were defined according to therapeutic ranges. Inter- and intra-assay precisions values were less than 15 %. After validation, this method was successfully applied in daily practice for therapeutic drug monitoring of polymedicated psychiatric patients. ConclusionWe developed and validated one of the most sensitive and complete UPLC-MS/MS methods in psychopharmacology, allowing the simultaneous determination of 55 psychotropic drugs in only 5.7 min after a simple sample preparation. This method has been successfully used in daily practice for therapeutic drug monitoring of psychiatric patients and is especially useful in polymedicated patients.

Model-based dosing optimization and therapeutic drug monitoring practices of teicoplanin in patients with complicated or non-complicated methicillin-resistant staphylococcus aureusinfection.

This study aims to establish a population pharmacokinetic (PK) model of teicoplanin in Chinese adult patients to evaluate the dosing regimen in the label sheet and optimize it. Nonlinear mixed-effects modelling was used to estimate PK parameters. Monte Carlo simulations were used to evaluate the attainment of various dosing regimens in achieving the target trough concentrations in patients with normal or decreased renal function. A total of 115 patients were enrolled in this retrospective study. Creatinine clearance (CrCL) and albumin (ALB) were identified as covariates on the clearance of teicoplanin. For the treatment of non-complicated methicillin-resistant Staphylococcus aureus (MRSA) infections in patients with normal renal function and serum ALB concentration, the recommended dosing regimen was 600 mg q12h with five administrations as the loading dose followed by 600 mg qd as the maintenance dose; for the treatment of serious and/or complicated MRSA infections, the recommended dosing regimen was 800 mg q12h with five administrations as the loading dose followed by 800 mg qd as the maintenance dose. It is worth noting that both the loading and maintenance doses ought to be modified based on the patient's renal function and serum ALB concentration. In addition, trough concentrations of teicoplanin were significantly increased every other week. Both loading dosing and maintenance dosing regimens were recommended to be adjusted according to patient's renal function and serum ALB concentration. In addition, it is necessary to perform follow-up therapeutic drug monitoring of teicoplanin at least once every week.

Therapeutic drug monitoring in India: A strength, weakness, opportunity and threats analysis.

Over the last three to four decades, Therapeutic Drug Monitoring (TDM) has shaped itself as therapeutic drug management, an integral component of precision medicine. The practice of TDM is not extensive in India, despite being one of the fastest-growing economies in the world. It is currently limited to a few academic medical centres and teaching hospitals. Apart from the immunosuppressive drugs, several other therapeutic areas, such as anticancer, antifungal, antibiotic and antitubercular, have demonstrated great potential to improve patient outcomes in Indian settings. Factors such as the higher prevalence of nutritional deficiencies, tropical diseases, widespread use of alternative medicines, unalike pharmacogenomics and sparse population-specific data available on therapeutic ranges of several drugs make the population of this subcontinent unique regarding the relevance of TDM. Despite the impact of TDM in clinical science and its widespread application, TDM has failed to receive the attention it deserves in India. This review intends to bring out a strength, weakness, opportunity and threats (SWOT) analysis for TDM in India so that appropriate steps for fostering the growth of TDM could be envisioned. The need of the hour is the creation of a cooperative group including all the stakeholders, such as TDM professionals, clinicians and the government and devising a National Action Plan to strengthen TDM. Nodal TDM centres should be established, and pilot programmes should be rolled out to identify the thrust areas for TDM in the country, capacity building and creating awareness to integrate TDM into mainstream clinical medicine.

Feasibility of individualised patient modelling for continuous vancomycin infusions in outpatient antimicrobial therapy, a retrospective study.

The area under the curve (AUC) to minimum inhibitory concentration (MIC) ratio is proposed as a therapeutic drug-monitoring parameter for dosing vancomycin continuous infusion in methicillin-resistant Staphylococcus aureus (MRSA) infection. Individualised pharmacokinetic-pharmacodynamic (PK/PD) calculation of AUC24 may better represent therapeutic dosing than current Therapeutic Drug Monitoring (TDM) practices, targeting a Steady State Concentration of 15-25mg/L. To compare real world TDM practice to theoretical, individualised, PK/PD target parameters utilising Bayesian predictions to steady state concentrations (Css) for outpatients on continuous vancomycin infusions. A retrospective single centre study was conducted at a tertiary hospital on adult patients, enrolled in an outpatient parenteral antimicrobial therapy (OPAT) program, receiving vancomycin infusions for MRSA infection. Retrospective Bayesian dosing was modelled to target PK/PD parameters and compared to real world data. Fifteen patients were evaluated with 53% (8/15) achieved target CSS during hospitalisation, and 83% (13/15) as outpatient. Median Bayesian AUC/MIC was 613mg.h/L with CSS 25mg/L. Patients suffering an Acute Kidney Injury (33%) had higher AUC0-24/MIC values. Retrospective Bayesian modelling demonstrated on median 250mg/24h lower doses than that administered was required (R2 = 0.81) which achieved AUC24/MIC median 444.8 (range 405-460) mg.h/L and CSS 18.8 (range 16.8-20.4) mg/L. Bayesian modelling could assist in obtaining more timely target parameters at lower doses for patients receiving continuous vancomycin infusion as part of an OPAT program, which may beget fewer adverse effects. Utilisation of personalised predictive modelling may optimise vancomycin prescribing, achieving earlier target concentrations as compared to empiric dosing regimens.

From "wet" matrices to "dry" blood spot sampling strategy: a versatile LC-MS/MS assay for simultaneous monitoring caffeine and its three primary metabolites in preterm infants.

To update traditional "wet" matrices to dried blood spot (DBS) sampling, based on the liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) technique, and develop a method for simultaneous analyzing caffeine and its three primary metabolites (theobromine, paraxanthine, and theophylline), supporting routine therapeutic drug monitoring (TDM) for preterm infants. DBS samples were prepared by a two-step quantitative sampling method, i.e.,volumetric sampling of a quantitative 10 μL volume of peripheral blood and an 8 mm diameter whole punch extraction by a methanol/water (80/20, v/v) mixture containing 125 mM formic acid. Four paired stable isotope labeled internal standards and a collision energy defect strategy were applied for the method optimization. The method was fully validated following international guidelines and industrial recommendations on DBS analysis. Cross validation with previously developed plasma method was also proceeded. The validated method was then implemented on the TDM for preterm infants. The two-step quantitative sampling strategy and ahigh recovery extraction method were developed and optimized. The method validation results were all within the acceptable criteria. Satisfactory parallelism, concordance, and correlation were observed between DBS and plasma concentrations of the four analytes. The method was applied to provide routine TDM services to 20 preterm infants. A versatile LC-MS/MS platform for simultaneous monitoring caffeine and its three primary metabolites was developed, fully validated, and successfully applied into the routine clinical TDM practices. Sampling method switching from "wet" matrices to "dry" DBS will facilitate and support the precision dosing of caffeine for preterm infants.

Vancomycin Therapeutic Drug Monitoring: A Cross-Sectional Survey of Canadian Hospitals.

Little is known about the current landscape of vancomycin therapeutic drug monitoring (TDM) in Canadian hospitals, which operate within publicly funded health care systems. To determine current TDM practices for vancomycin and associated challenges and to gather perceptions about TDM based on area under the concentration-time curve (AUC) in Canadian hospitals. An electronic survey was distributed to hospital pharmacists in spring 2021 through multiple national and provincial antimicrobial stewardship, public health, and pharmacy organizations. The survey gathered data about hospital characteristics, TDM methods, inclusion criteria for patient selection, pharmacokinetic and pharmacodynamic targets, vancomycin susceptibility testing and reporting, and perceived barriers and challenges. In total, 120 pharmacists from 10 of the 13 provincial and territorial jurisdictions in Canada, representing 12.5% of Canadian acute care hospitals (n = 962), completed at least 90% of survey questions. The predominant TDM method was trough-based (107/119, 89.9%); another 10.1% of respondents (12/119) reported performing AUC-based TDM (with or without trough-based TDM), and 17.9% (19/106) of those not already using AUC-based TDM were considering implementing it within 1 to 2 years. Among hospitals performing trough-based TDM, 60.5% (66/109) targeted trough levels between 15 and 20 mg/L for serious infections with methicillin-resistant Staphylococcus aureus. One-quarter of the respondents using this method (27/109, 24.8%) agreed that trough-based TDM was of uncertain benefit, and about one-third (33/109, 30.3%) were neutral on this question. Multiple challenges were identified for trough-based TDM, including sub- or supra-therapeutic concentrations and collection of specimens at inappropriate times. Overall, 40.5% (47/116) of respondents agreed that AUC-based TDM was likely safer than trough-based TDM, whereas 23.3% (27/116) agreed that AUC-based TDM was likely more effective. This survey represents a first step in developing evidence-based, standardized best practices for vancomycin TDM that are uniquely suited to the Canadian health care system.

Precision Oncology by Point-of-Care Therapeutic Drug Monitoring and Dosage Adjustment of Conventional Cytotoxic Chemotherapies: A Perspective.

Therapeutic drug monitoring (TDM) of conventional cytotoxic chemotherapies is strongly supported yet poorly implemented in daily practice in hospitals. Analytical methods for the quantification of cytotoxic drugs are instead widely presented in the scientific literature, while the use of these therapeutics is expected to keep going for longer. There are two main issues hindering the implementation of TDM: turnaround time, which is incompatible with the dosage profiles of these drugs, and exposure surrogate marker, namely total area under the curve (AUC). Therefore, this perspective article aims to define the adjustment needed from current to efficient TDM practice for cytotoxics, namely point-of-care (POC) TDM. For real-time dose adjustment, which is required for chemotherapies, such POC TDM is only achievable with analytical methods that match the sensitivity and selectivity of current methods, such as chromatography, as well as model-informed precision dosing platforms to assist the oncologist with dose fine-tuning based on quantification results and targeted intervals.

Implementing Vancomycin Population Pharmacokinetic Models: An App for Individualized Antibiotic Therapy in Critically Ill Patients.

In individualized therapy, the Bayesian approach integrated with population pharmacokinetic models (PopPK) for predictions together with therapeutic drug monitoring (TDM) to maintain adequate objectives is useful to maximize the efficacy and minimize the probability of toxicity of vancomycin in critically ill patients. Although there are limitations to implementation, model-informed precision dosing (MIPD) is an approach to integrate these elements, which has the potential to optimize the TDM process and maximize the success of antibacterial therapy. The objective of this work was to present an app for individualized therapy and perform a validation of the implemented vancomycin PopPK models. A pragmatic approach was used for selecting the models of Llopis, Goti and Revilla for developing a Shiny app with R. Through ordinary differential equation (ODE)-based mixed effects models from the mlxR package, the app simulates the concentrations' behavior, estimates whether the model was simulated without variability and predicts whether the model was simulated with variability. Moreover, we evaluated the predictive performance with retrospective trough concentration data from patients admitted to the adult critical care unit. Although there were no significant differences in the performance of the estimates, the Llopis model showed better accuracy (mean 80.88%; SD 46.5%); however, it had greater bias (mean -34.47%, SD 63.38%) compared to the Revilla et al. (mean 10.61%, SD 66.37%) and Goti et al. (mean of 13.54%, SD 64.93%) models. With respect to the RMSE (root mean square error), the Llopis (mean of 10.69 mg/L, SD 12.23 mg/L) and Revilla models (mean of 10.65 mg/L, SD 12.81 mg/L) were comparable, and the lowest RMSE was found in the Goti model (mean 9.06 mg/L, SD 9 mg/L). Regarding the predictions, this behavior did not change, and the results varied relatively little. Although our results are satisfactory, the predictive performance in recent studies with vancomycin is heterogeneous, and although these three models have proven to be useful for clinical application, further research and adaptation of PopPK models is required, as well as implementation in the clinical practice of MIPD and TDM in real time.

The impact of daptomycin therapeutic drug monitoring on clinical outcomes: a systematic review

AimDaptomycin therapeutic drug monitoring (TDM) is a potentially valuable intervention for a relatively new drug. The aim of this study was to determine whether daptomycin TDM, including dose adjustment where necessary, improves the clinical outcomes of adult patients with Gram-positive infections. MethodsA systematic review of English-language studies in MEDLINE (Ovid MEDLINE and Epub Ahead of Print, In-process, In-Data-Review & Other Non-Indexed Citations, Daily and Versions), EMBASE via OVID, Cochrane Central Register of Controlled Trials via the OVID platform, Scopus and Web of Science online databases was performed and conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. There was no discrimination on study type or time of publication. Study selectionAdults (age ≥18 years) with a Gram-positive infection requiring treatment with daptomycin who received TDM, with subsequent reporting of serum concentrations and dose adjustment where necessary, were included. ResultsIn total, 2869 studies were identified, of which nine met the inclusion criteria. No studies of daptomycin TDM including a relevant control arm have been published to date. All of the included studies were single-arm observational cohort studies. Broad heterogeneity was observed between the studies in terms of included pathogens, infection types, daptomycin TDM practices, reported clinical outcomes, and reporting of potential confounders. ConclusionsNo studies exploring the efficacy of routine daptomycin TDM on patient-centred outcomes in comparison with fixed dosing regimens have been published to date. This represents a key knowledge gap as opposed to an inherent lack of efficacy. Further well-designed, comparative studies are required to determine the role of daptomycin TDM in patients with Gram-positive infections.

Is there a multinational consensus of tobramycin prescribing and monitoring for cystic fibrosis? Survey of current therapeutic drug monitoring practices in USA/Canada, UK/Ireland, and Australia/New Zealand

ObjectivesSophisticated scientific methods have facilitated dose individualisation with substantial advancements in therapeutic drug monitoring (TDM) practice. It is unclear whether these methods have translated to the clinical setting. This study...

Therapeutic drug monitoring of free vancomycin concentration in practice: a new analytical technique based on the HFCF-UF sample separation method.

To establish a method for free vancomycin concentration determination in human plasma and apply it to clinical therapeutic drug monitoring (TDM). The unbound vancomycin in plasma was separated by the hollow fiber centrifugal ultrafiltration (HFCF-UF) technique and analyzed by HPLC. Chromatographic conditions were optimized, the specificity, linearity, precision, recovery, and stability of the method were examined, and plasma samples of patients were measured. The standard curve for free vancomycin is Y=0.0277X-0.0080 with good linearity within 0.25-50μg·mL-1 . The relative and absolute recovery rates for vancomycin were 98.63%-101.0% and 88.41%-101.2%, respectively. The intraday and interday precision RSD were less than 10%. Plasma was stable under several conditions. The TDM value of the free vancomycin concentration of 20 patients was 0.99-38.51μg·mL-1 , and the correlation between the free and total concentrations was not significant. The unbound fraction of vancomycin ranged 25.5% - 84.8%, with large variation. The operation of free vancomycin separation by HFCF-UF was simple and suitable for TDM in practice. The unbound fraction of vancomycin in clinical samples varied significantly between individuals. It is recommended to perform free concentration TDM in critically ill patients.

Evaluation of drug prescribing patterns and therapeutic drug monitoring practice using electronic medical records.

Therapeutic drug monitoring (TDM) is performed for drugs with narrow therapeutic indices. At Seoul National University Hospital (SNUH) and Seoul National University Bundang Hospital (SNUBH), TDM services are provided for various drugs such as antibiotics and antiepileptics. This study aimed to identify prescription patterns over time using electronic medical records and analyze their relationship with TDM practice. Data were collected from a clinical data warehouse from 2007 to 2020, and the number of patients, total number of drug administration days, serum level tests, and TDM were calculated. The ratio was calculated as the number of serum level tests or TDM to the total number of drug administration days. The study included 136,427 and 162,927 patients from SNUH and SNUBH who were prescribed 11 specified drugs. Each drug showed different prescription patterns over time, and the serum level test and TDM also changed with prescription pattern changes. Serum level test or TDM of antibiotics was frequently used compared to antiepileptics. As some drugs' usage and test for drugs have decreased newly developed drugs are replacing old drugs. It is recommended that TDM services include these new drugs as well for an effective and safe therapy.

Knowledge and Attitude of Healthcare Practitioners Toward Therapeutic Drug Monitoring Practices in the Najran Region, Kingdom of Saudi Arabia.

Therapeutic drug monitoring (TDM) is one of the useful clinical tools that aim to improve and ensure the best therapeutic effects while avoiding drug-related toxicity. We aimed to evaluate the knowledge and attitude toward TDM practices among healthcare practitioners in the Najran region, Saudi Arabia. A cross-sectional study was conducted between May 2021 and October 2021 for assessing the awareness and attitude of licensed doctors and pharmacists working in Saudi Arabiaregarding TDM practices. A 31-item questionnaire was distributed to the healthcare professionals via an electronic link.Descriptive and inferential statistics were used to report the data. A total of 392 participants submitted questionnaires. More than half of the professionals (55.9%) had an overall awareness of the TDM, while only 3.1% did not. Only 16% and 23% of those who were surveyed indicated that TDM is used at the beginning of medication administration and when shifting from one drug to another, respectively. The majority of the professionals responded that TDM is revealed with laboratory changes in liver and kidney function (81%), and TDM is specified with suspected therapeutic failure (93%). Only half of the respondents claimed that they had ever requested or suggested a TDM in their practice. More than 90% of the respondents claimed that they were aware of the indications for vancomycin (n = 381), gentamicin (n = 375), lithium (n = 369), digoxin (n = 380), and theophylline (n = 369). This study found that the majority of the healthcare professionals in Najran were aware of the TDM, particularly those with more than 10 years of professional experience. In addition, TDM service is not widely available in smaller hospitalsin Najran. There is a need to conduct customized training programs for junior healthcare professionals, thus increasing the levels of awareness toward TDM. Future studies in Saudi Arabia can explore the role of clinical pharmacists in the provision of TDM services by assessing the clinical and economic outcomes of pharmacist interventions in TDM.

Therapeutic Drug Monitoring in Practice for Inflammatory Bowel Disease.

To outline the development, rationale, and practical use of therapeutic drug monitoring in patients with inflammatory bowel disease. Therapeutic drug monitoring is traditionally discussed in terms of a proactive or reactive approach. However, these terms are not always consistently defined and can be confusing when translating research to clinical practice. Personalized approaches incorporating clinical context and precision medicine are emerging. Personalized therapeutic drug monitoring combines a structured and proactive strategy for monitoring biologic concentrations as well as identification of antidrug antibody development or subtherapeutic dosing in the setting of loss of response. Optimizing biologic therapy can improve outcomes and avoid loss of response. Why, when, and how we measure drug troughs and anti-drug antibodies is a moving target, though what is known is that the appropriate and evidence-based use of this practice prevents adverse events and improves outcomes in patients with inflammatory bowel disease.

Population Pharmacokinetic Analysis Proves Superiority of Continuous Infusion in PK/PD Target Attainment with Oxacillin in Staphylococcal Infections.

Considering its very short elimination half-life, the approved oxacillin dosage might not be sufficient to maintain the pharmacokinetic/pharmacodynamics (PK/PD) target of time-dependent antibiotics. This study aimed to describe the population pharmacokinetics of oxacillin and to explore the probability of PK/PD target attainment by using various dosing regimens with oxacillin in staphylococcal infections. Both total and unbound oxacillin plasma concentrations retrieved as a part of routine therapeutic drug-monitoring practice were analyzed using nonlinear mixed-effects modeling. Monte Carlo simulations were used to generate the theoretical distribution of unbound oxacillin plasma concentration-time profiles at various dosage regimens. Data from 24 patients treated with oxacillin for staphylococcal infection have been included into the analysis. The volume of distribution of oxacillin in the population was 11.2 L, while the elimination rate constant baseline of 0.73 h-1 increased by 0.3 h-1 with each 1 mL/s/1.73 m2 of the estimated glomerular filtration rate (eGFR). The median value of oxacillin binding to plasma proteins was 86%. The superiority of continuous infusion in achieving target PK/PD values was demonstrated and dosing according to eGFR was proposed. Daily oxacillin doses of 9.5 g, 11 g, or 12.5 g administered by continuous infusion have been shown to be optimal for achieving target PK/PD values in patients with moderate, mild, or normal renal function, respectively.

Therapeutic drug monitoring practices of anti-infectives: An Asia-wide cross-sectional survey.

Objectives: The current practice of therapeutic drug monitoring (TDM) in Asia is poorly documented. Our aim was to capture and describe TDM services delivered in hospitals across Asia, including aspects such as assay availability, interpretation of results and clinical decision-making. Methods: An online survey about anti-infective TDM practices, available in English and involving 50 questions, was promoted to people involved in TDM in Asia. The survey was open for responses from September to November 2021. Results: Of 207 responses from participants working in 14 Asian countries, 150 responses from 10 countries could be included. TDM services are available for many anti-infectives, providing assays based on chromatographic assays (100.0%) or immunoassays (39.3%). Clinicians (82.6%) and pharmacists (86.8%) were responsible for ordering and interpreting TDM. Most services provided reference targets and dose recommendations. Interpretative support was available to a varying degree. Assay results were available and clinical decision-making could be completed within 24 h in most hospitals (87.9% and 88.9% respectively). As the turnaround time of assay results decreased, the proportion of clinical decision-making completed within 8 h increased. Barriers to implementation of TDM included lack of funding or equipment (71.1%), lack of clinician interest or cooperation (47.0%), and lack of expertise (42.3%). Lack of expertise was the primary barrier for using precision dosing software (50.5%). Conclusion: There are significant differences and challenges in the development and practice of anti-infective TDM in Asian countries.

A Systematic Review of the Effect of Therapeutic Drug Monitoring on Patient Health Outcomes during Treatment with Carbapenems.

Adjusting dosing regimens based on measurements of carbapenem levels may improve carbapenem exposure in patients. This systematic review aims to describe the effect carbapenem therapeutic drug monitoring (TDM) has on health outcomes, including the emergence of antimicrobial resistance (AMR). Four databases were searched for studies that reported health outcomes following adjustment to dosing regimens, according to measurements of carbapenem concentration. Bias in the studies was assessed with risk of bias analysis tools. Study characteristics and outcomes were tabulated and a narrative synthesis was performed. In total, 2 randomised controlled trials (RCTs), 17 non-randomised studies, and 19 clinical case studies were included. Significant variation in TDM practice was seen; consequently, a meta-analysis was unsuitable. Few studies assessed impacts on AMR. No significant improvement on health outcomes and no detrimental effects of carbapenem TDM were observed. Five cohort studies showed significant associations between achieving target concentrations and clinical success, including suppression of resistance. Studies in this review showed no obvious improvement in clinical outcomes when TDM is implemented. Optimisation and standardisation of carbapenem TDM practice are needed to improve intervention success and enable study synthesis. Further suitably powered studies of standardised TDM are required to assess the impact of TMD on clinical outcomes and AMR.